Department of Clinical Immunology, Meiji Pharmaceutical University, Tokyo, Japan.
J Pharm Pharm Sci. 2020;23(1):86-99. doi: 10.18433/jpps30847.
Langerhans cells (LCs) polarize the immune milieu towards a T helper type (Th) 1 or Th2 immune response. We investigated the effects of selected tetracyclines on Th cells development mediated by LCs, and their implications for the treatment of atopic dermatitis (AD).
Mice were primed with ovalbumin (OVA) peptide-pulsed LCs, which had been treated with each antibiotic, via the hind footpad. After 5 days, the Th1/Th2 cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The therapeutic effects of a selected antibiotic on AD-like skin lesions of NC/Nga mice were assessed in terms of the skin severity score, histological changes in the lesioned skin, the serum level of total IgE, and expression of Th1/Th2 cytokines in lymph nodes and skin lesions.
Antibiotic-treated, OVA peptide-pulsed LCs inhibited development of Th2 cells but not Th1 cells. This was accompanied by suppression of T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs. Doxycycline had the greatest activity against Staphylococcus aureus strains isolated from skin lesions of patients with AD, and a strong inhibitory effect on Th2 cell development. Doxycycline suppressed the increase in the skin severity score during the acute phase in NC/Nga mice similar to betamethasone. This suppressive effect was associated with a decrease in the serum IgE level and production of Th2 cytokines in auricular lymph node cells and skin lesions.
Topical application of doxycycline to AD lesions would act on both superficial S. aureus colonization and epidermal LCs, thus possibly inhibiting the development of Th2 cells in vivo, with benefits for control of acute inflammation in AD.
朗格汉斯细胞（LCs）使免疫环境向辅助性 T 细胞（Th）1 或 Th2 免疫反应极化。我们研究了选定的四环素类药物对 LCs 介导的 Th 细胞发育的影响，及其对特应性皮炎（AD）治疗的意义。
通过后足底给小鼠用经各抗生素处理的卵清蛋白（OVA）肽脉冲 LC 进行致敏。5 天后，通过酶联免疫吸附试验检测腘淋巴结中的 Th1/Th2 细胞因子反应。使用逆转录聚合酶链反应（RT-PCR）检测 LC 表面分子的表达。通过评估选定抗生素对 NC/Nga 小鼠类似 AD 皮肤损伤的皮肤严重程度评分、损伤皮肤的组织学变化、血清总 IgE 水平以及淋巴结和皮肤损伤中 Th1/Th2 细胞因子的表达，评估抗生素的治疗效果。
经抗生素处理的 OVA 肽脉冲 LC 抑制了 Th2 细胞的发育，但不抑制 Th1 细胞。这伴随着 LC 中 T 细胞免疫球蛋白和粘蛋白结构域蛋白（TIM）-4 表达的抑制。强力霉素对分离自 AD 患者皮损的金黄色葡萄球菌菌株最具活性，对 Th2 细胞发育具有很强的抑制作用。强力霉素抑制了 NC/Nga 小鼠在急性期皮肤严重程度评分的增加，与倍他米松相似。这种抑制作用与血清 IgE 水平降低以及耳廓淋巴结细胞和皮肤损伤中 Th2 细胞因子的产生减少有关。
强力霉素局部应用于 AD 病变可作用于表皮金黄色葡萄球菌定植和表皮 LCs，从而可能抑制体内 Th2 细胞的发育，有利于控制 AD 的急性炎症。
